In a modern society, a number of diseases are able to be easily cured, and there are few incurable diseases. However, cancer requires very difficult and complex therapies unlike treatments for other diseases, and even the complex therapies are not fully effective. Currently, a method used for cancer therapy is largely divided into surgery, radiation therapy, and chemotherapy. Cancer patients receive surgery to remove cancers, wherein when the cancer does not spread far but is only localized, the cancer is able to be completely cured only by the surgery. However, it tends to cause cancer metastasis in over 70% of patients, and thus, adjuvant therapies are accompanied with the surgery. As one of the adjuvant therapies, radiation therapy is a therapy that kills cancer cells by using high-energy radiation. When the cancer cells are treated with radiation, the radiation therapy is not able to immediately kill the cancer cells, but destroys a proliferation function of the cancer cells, thereby preventing production of new cancer cells and further division. However, this method has an adverse effect since it affects normal cells as well as the cancer cells. Chemotherapy is also an adjuvant therapy that kills the cancer cells using medicine after surgery, and is performed to kill invisible cancer cells. However, chemotherapy may also have side effects such as vomiting, diarrhea, hair loss, etc.
In order to minimize these adverse side effects, immunotherapy has emerged in recent years. Further, as described above, since the cancer metastasis rate is over 70% of total patients, it is considered that treatment of metastatic cancer is essential in completely curing the cancer, and thus, immunotherapy is a very effective treatment method.
The immunotherapy is a method of treating the cancer by using an immune response in the patient's body. The immunotherapy method may eventually achieve cancer prevention. The cancer immunotherapy is a method in which an antigen which is a cause of cancer is administered to activate cancer-specific immune cells, and then, the activated immune cells specifically attack the cancer in the body, thereby inducing treatment according to a principle of vaccines. Further, when the cancer-specific antigen is administered in a patient's body that does not suffer from cancer, the immune cells that were not activated become activated to be cancer-specific immune memory cells, and when the patient suffers from the cancer, the cells specifically attack the cancer cells.
For cancer immunotherapy, it is important to transport the cancer-specific antigen to a lymph node in which the immune cells are concentrated. Further, since a material needs to be injected into the body, toxicity in the body should be considered.
However, the existing attempts to transport only the cancer-specific antigen itself to the lymph node have not been significantly effective. The reason is that a strong immune response is not generated in the body due to a short length of cancer-specific antigen peptide (Xu, Z. et al., J. Control. Release Vol. 172, pp. 259-265, 2011; Jewel, C. M., et al., Proc. Natl. Acad. Sci. USA Vo. 108, 15745-15750, 2011).
Further, polymers have been widely used as an in vivo carrier of the cancer-specific antigen, and when cancer antigen is immobilized onto a surface of the polymer for in vivo transportation of the antigen, it needs to expose the cancer-specific antigen onto a particle surface by using a chemical bond. However, this method of using the polymer has a limitation in uniformly exposing the antigen with high density.
Ferritin is formed of 24 identical protein subunits consisting of heavy chains and light chains, and forms a hollow shell in a living body. The protein binding to iron has an iron storage function, and an iron detoxification function (Harrison et al., Biochim Biophys Acta., 1275(3): 161-163, 1996). The protein maintains iron balance in cells for growth and survival of most tissues, and functions as a cell protective protein that minimizes formation of oxygen-free radical due to the binding with the iron in the cells (Lawson et al., Nature, 349: 541-544, 1991). The ferritin has a molecular weight of about 500,000 Da, consists of heavy chains and light chains, and has a self-assembly capability to show unique property in which spherical particles are formed.
Therefore, the present inventors made an effort to develop a method of effectively transporting a cancer-specific antigen to a lymph node, and as a result, found that when an expression vector encoding a human ferritin protein monomer fused with a cancer-specific epitope was designed and produced, and expressed in E. coli, a protein nanoparticle in which the cancer-specific epitope was expressed on a surface of the protein nanoparticle was developed, the protein nanoparticle had a remarkable lymph node targeting capability, and also had a remarkable effect for cancer immunotherapy due to the lymph node targeting capability, as compared to the existing nanoparticles, and completed the present invention.